Goal 1) examine and characterize both common and rare craniofacial anomalies through technologies including 3D imaging and genomic analysis to allow us to diagnosis, predict, and treat these conditions. We have collaborated with various clinical research teams to begin characterizing their patient cohorts for craniofacial and oral dysmorphology. We have a Natural History Craniofacial Anomalies protocol to allow for conducting comprehensive assessments and analyses to correlate phenotype and genotype. Through these protocols, we are examining and comparing the craniofacial dysmorphologies across genetic mutations to understand the development of the facial and the influences that result in dysmorphologies. We are developing a craniofacial database that includes 3D imaging modalities. Using a TGFbeta receptor 2 KI mouse model, we have identified potential downstream effects that result in tooth and craniofacial developmental anomalies that have also been identified in patients. Goal 2) study bone regeneration to determine the mechanisms that distinguish bone regeneration in various environments. We have approved small animal protocols that will allow further examination of bone marrow stromal/stem cell function in the various aging environments. We have a second small animal protocol that examines a preclinical model of spontaneous bone regeneration and the influence of the aging environment. In each of these preclinical models, we are examining temporal and age-related RNA sequence variations to determine the the role of the microniche and its impact on the osteoprogenitors/BMSCs.